Our global hypothesis is that two-way exchanges between Human Core (housing clinical databases and patient samples) with mechanistic studies of inflammatory signaling will help us devise THERAPY FOR TRAUMA PRIMED CELLS. Since initial funding in 1993, our MOF databases have grown substantially to yield novel insights into fundamental problems inherent to (I) hemorrhagic shock, (II), transfusion (III), mechanisms of anti-inflammatory resuscitation. The projects remain highly dependent on each other, and invite the Human Core to further test hypotheses. Project. I focuses on lung injury induced by the cytotoxic properties of mesenteric lymph that occur after hemorrhagic shock, presumably due to eicosanoid metabolism. In this proposal we expand on the potential bioactivity of this lymph, the condition necessary for its toxicity, and dissect its components. Project. II undertakes a detailed analysis of lipids and proteins accruing in blood products, focusing on the acute coagulopathy of trauma with the aim of minimizing mortality by proper blood resuscitation. Project. Ill examines mechanism of reducing inflammation by regulating transcription factor activation with hypertonic solution and seeks to apply inhaled hypertonic saline to reduce lung inflammation in animals and humans. To validate these ideas, the Human Core is charged with supplying specimens, gathering data, and updating the Trauma MOF database while remaining in strict regulatory compliance. A vigorous Cell, Imaging & Proteomics Core will provide each project with commonly used human cells, equipment and expertise to perform advanced molecular colocalization and cytometry using antibodies as well and advanced MS proteomics . These efforts are supported by a seasoned Administrative Core that seeks to further the prowess of our three institutions (Denver Health Medical Center, Belle Bonfils Blood Center, University of Colorado Health Sciences Center) to promulgate Trauma Research and improve patient care.